Repeatedly bred male and female rats develop arteriosclerosis spontaneously. The early arterial lesions consist of intimal mucopolysaccharide accumulations which become capped-over by collagen, i.e., fibrotic plaques. With continued breeding and progressively advancing arteriosclerosis, there are medial ground substance alterations, elastolytic changes, and eventual calcification. There is a distinct sex dichotomy in that male breeders develop microscopic aortic lesions, but die significantly earlier than the female breeders which develop advanced grossly-visible arteriosclerosis. Emphasis will be placed on the biochemical alterations of aortic mucopolysaccharides during the early pathogenesis of arteriosclerosis and relative to development of the fibrous plaques and advanced complications. Detailed studies of the mucopolysaccharide metabolism in these arterosclerotic aortae will be done using such parameters as aortic glucosamine and galactosamine, along with identification of mucopolysaccharide, e.g., specific chondroitin sulfates. Isotopes will be used to define the dynamics of aortic ground substance metabolism. Similarly, the metabolism or aortic collagen and elastin will be investigated using proline hydroxylase and elastolytic enzyme activity as indices of fibrosis and elastosis. The tendency of the advanced lesions to become calcified will be investigated relative to alterations in calcium and phosphate as well as acid and alkaline phosphatases - all of which will be related to the levels of these same constituents in the blood. Special emphasis will be placed on the correlation of the abnormal hormonal alterations which attend repeated breeding with the aberrant connective tissue metabolism and pathogenesis of arteriosclerosis.